Medical Biophysics Commons^™

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations and Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Development Of Advanced Mr-Guided Adaptive Radiation Therapy Methods For Head & Neck Cancers On The 1.5t Mr-Linac, Brigid Mcdonald

Dissertations and Theses (Open Access)

The 1.5T hybrid MRI/linear accelerator (MR-linac) has recently been introduced into clinical practice and used for the treatment of head and neck cancers (HNC). This device enables on-line adaptive radiation therapy (ART) based on anatomical changes throughout treatment and variations in patient position. This novel technology also has the potential for advanced ART strategies such as dose-optimized ART, in which the treatment plan is optimized based on the accumulated dose over previous fractions, or biological image-guided ART, in which the plan is adapted based on individual tumor response as measured through quantitative imaging techniques such as diffusion-weighted imaging (DWI). The …

Seizure Prediction In Epilepsy Patients, Gary Dean Cravens

NSU REACH and IPE Day

Purpose/Objective: Characterize rigorously the preictal period in epilepsy patients to improve the development of seizure prediction techniques. Background/Rationale: 30% of epilepsy patients are not well-controlled on medications and would benefit immensely from reliable seizure prediction. Methods/Methodology: Computational model consisting of in-silico Hodgkin-Huxley neurons arranged in a small-world topology using the Watts-Strogatz algorithm is used to generate synthetic electrocorticographic (ECoG) signals. ECoG data from 18 epilepsy patients is used to validate the model. Unsupervised machine learning is used with both patient and synthetic data to identify potential electrophysiologic biomarkers of the preictal period. Results/Findings: The model has shown states corresponding to …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

A Retrospective Dosimetry Comparison To Define Uncertainties Found In A Novel Intensity Modulated Electron Therapy (Imet) Treatment Technique For Use In Radiation Therapy, Marco A. Masciantonio

Honors Undergraduate Theses

This study will investigate the difference in radiation at different volumes between traditional electron beam therapy and a novel IMET. The difference in dose will be recorded between the novel IMET and the IMET with a slight shift in the target area. The percent difference between this new model treatment and the model treatment with a shift will be calculated. The main goal of this project is to determine if the target area is still sufficiently treated with this slight shift of the patient in different directions. The percent difference is crucial for the success of this project. It will …

Biophysical Characterization Of Light-Gated Ion Channels Using Planar Automated Patch Clamp, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins (ChRs) are proteins that guide phototaxis in protists and exhibit light-gated channel conductance when their genes are heterologously expressed in mammalian cells. ChRs are widely used as molecular tools to control neurons and cardiomyocytes with light (optogenetics). Cation- and anion-selective ChRs (CCRs and ACRs, respectively) enable stimulation and inhibition of neuronal activity by depolarization and hyperpolarization of the membrane, respectively. More than 400 natural ChR variants have been identified so far, and high-throughput polynucleotide sequencing projects add many more each year. However, electrophysiological characterization of new ChRs lags behind because it is mostly done by time-consuming manual patch clamp …

Putative Concussion Biomarkers Identified In Adolescent Male Athletes Using Targeted Plasma Proteomics, Michael R. Miller, Michael Robinson, Lisa Fischer, Alicia Dibattista, Maitray A. Patel, Mark Daley, Robert Bartha, Gregory A. Dekaban, Ravi S. Menon, J. Kevin Shoemaker, Eleftherios P. Diamandis, Ioannis Prassas, Douglas D. Fraser

Medical Biophysics Publications

Sport concussions can be difficult to diagnose and if missed, they can expose athletes to greater injury risk and long-lasting neurological disabilities. Discovery of objective biomarkers to aid concussion diagnosis is critical to protecting athlete brain health. To this end, we performed targeted proteomics on plasma obtained from adolescent athletes suffering a sports concussion. A total of 11 concussed male athletes were enrolled at our academic Sport Medicine Concussion Clinic, as well as 24 sex-, age- and activity-matched healthy control subjects. Clinical evaluation was performed and blood was drawn within 72 h of injury. Proximity extension assays were performed for …

Deep Convolutional Neural Networks For Accurate Diagnosis Of Covid-19 Patients Using Chest X-Ray Image Databases From Italy, Canada, And The Usa, Amgad A. Salama, Samy H. Darwish, Samir M. Abdel-Mageed, Radwa A. Meshref, Ehab I. Mohamed

The University of Louisville Journal of Respiratory Infections

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), famously known as COVID-19, has quickly become a global pandemic. Chest X-ray (CXR) imaging has proven reliable, fast, and cost-effective for identifying COVID-19 infections, which proceeds to display atypical unilateral patchy infiltration in the lungs like typical pneumonia. We employed the deep convolutional neural network (DCNN) ResNet-34 to detect and classify CXR images from patients with COVID-19 and Viral Pneumonia and Normal Controls.

Methods: We created a single database containing 781 source CXR images from four different international sub-databases: the Società Italiana di Radiologia Medica e Interventistica (SIRM), the GitHub Database, the …

Author Correction: Spread Of Pathological Tau Proteins Through Communicating Neurons In Human Alzheimer’S Disease (Nature Communications, (2020), 11, 1, (2612), 10.1038/S41467-020-15701-2), Jacob W. Vogel, Yasser Iturria-Medina, Olof T. Strandberg, Ruben Smith, Elizabeth Levitis, Alan C. Evans, Oskar Hansson, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Michael Donohue, Matthew Bernstein, Nick Fox, Paul Thompson

Medical Biophysics Publications

The original version of the Supplementary information associated with this Article inadvertently omitted Supplementary Table S1. The HTML has been updated to include a corrected version of the Supplementary information.

Correlation Between Alzheimer’S Disease And Type 2 Diabetes Using Non-Negative Matrix Factorization, Yeonwoo Chung, Hyunju Lee, Michael W. Weiner, Paul Aisen, Ronald Petersen, Cliford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Tamie Sather

Medical Biophysics Publications

Alzheimer’s disease (AD) is a complex and heterogeneous disease that can be affected by various genetic factors. Although the cause of AD is not yet known and there is no treatment to cure this disease, its progression can be delayed. AD has recently been recognized as a brain-specific type of diabetes called type 3 diabetes. Several studies have shown that people with type 2 diabetes (T2D) have a higher risk of developing AD. Therefore, it is important to identify subgroups of patients with AD that may be more likely to be associated with T2D. We here describe a new approach …

Higher Csf Stnfr1-Related Proteins Associate With Better Prognosis In Very Early Alzheimer’S Disease, William T. Hu, Tugba Ozturk, Alexander Kollhoff, Whitney Wharton, J. Christina Howell, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Richard J. Perrin, Leslie M. Shaw, Zaven Kachaturian, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Eliezer Masliah, Donna Masterman, Ozioma Okonkwo, Laurie Ryan, Nina Silverberg, Adam Fleisher

Medical Biophysics Publications

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and …

Kl-Vs Heterozygosity Is Associated With Lower Amyloid-Dependent Tau Accumulation And Memory Impairment In Alzheimer’S Disease, Julia Neitzel, Nicolai Franzmeier, Anna Rubinski, Martin Dichgans, Matthias Brendel, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles Decarli, Bret Borowski

Medical Biophysics Publications

Klotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShet showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VShet on tau-PET was stronger in Klotho mRNA-expressing brain …

Plasma Phosphorylated-Tau181 As A Predictive Biomarker For Alzheimer’S Amyloid, Tau And Fdg Pet Status, Xue Ning Shen, Yu Yuan Huang, Shi Dong Chen, Yu Guo, Lan Tan, Qiang Dong, Jin Tai Yu, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Jonathan Jackson, Eliezer Masliah, Donna Masterman, Ozioma Okonkwo

Medical Biophysics Publications

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = …

Repetitive Mild Traumatic Brain Injury In Mice Triggers A Slowly Developing Cascade Of Long-Term And Persistent Behavioral Deficits And Pathological Changes, Xiaoyun Xu, Matthew Cowan, Flavio Beraldo, Amy Schranz, Patrick Mccunn, Nicole Geremia, Zalman Brown, Maitray Patel, Karen L. Nygard, Reza Khazaee, Lihong Lu, Xingyu Liu, Michael J. Strong, Gregory A. Dekaban, Ravi Menon, Robert Bartha, Mark Daley, Haojie Mao, Vania Prado, Marco A.M. Prado, Lisa Saksida, Tim Bussey, Arthur Brown

Medical Biophysics Publications

We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. We sought to characterize the neuroimaging, cognitive, pathological and metabolomic changes in a mouse model of rmTBI. Using a closed-skull model of mTBI that when scaled to human leads …

Staging Tau Pathology With Tau Pet In Alzheimer’S Disease: A Longitudinal Study, Shi Dong Chen, Jia Ying Lu, Hong Qi Li, Yu Xiang Yang, Jie Hui Jiang, Mei Cui, Chuan Tao Zuo, Lan Tan, Qiang Dong, Jin Tai Yu, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Jonathan Jackson, Eliezer Masliah

Medical Biophysics Publications

A biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, …

Magnetic Resonance Imaging Sequence Identification Using A Metadata Learning Approach, Shuai Liang, Derek Beaton, Stephen R. Arnott, Tom Gee, Mojdeh Zamyadi, Robert Bartha, Sean Symons, Glenda M. Macqueen, Stefanie Hassel, Jason P. Lerch, Evdokia Anagnostou, Raymond W. Lam, Benicio N. Frey, Roumen Milev, Daniel J. Müller, Sidney H. Kennedy, Christopher J.M. Scott, Stephen C. Strother

Medical Biophysics Publications

Despite the wide application of the magnetic resonance imaging (MRI) technique, there are no widely used standards on naming and describing MRI sequences. The absence of consistent naming conventions presents a major challenge in automating image processing since most MRI software require a priori knowledge of the type of the MRI sequences to be processed. This issue becomes increasingly critical with the current efforts toward open-sharing of MRI data in the neuroscience community. This manuscript reports an MRI sequence detection method using imaging metadata and a supervised machine learning technique. Three datasets from the Brain Center for Ontario Data Exploration …

Neutrophil Dynamics Affect Mycobacterium Tuberculosis Granuloma Outcomes And Dissemination, Caitlin Hult, Joshua T. Mattila, Hannah P. Gideon, Jennifer J. Linderman, Denise E. Kischner

Math Faculty Publications

Neutrophil infiltration into tuberculous granulomas is often associated with higher bacteria loads and severe disease but the basis for this relationship is not well understood. To better elucidate the connection between neutrophils and pathology in primate systems, we paired data from experimental studies with our next generation computational model GranSim to identify neutrophil-related factors, including neutrophil recruitment, lifespan, and intracellular bacteria numbers, that drive granuloma-level outcomes. We predict mechanisms underlying spatial organization of neutrophils within granulomas and identify how neutrophils contribute to granuloma dissemination. We also performed virtual deletion and depletion of neutrophils within granulomas and found that neutrophils play …

Improved Segmentation Of The Intracranial And Ventricular Volumes In Populations With Cerebrovascular Lesions And Atrophy Using 3d Cnns, Emmanuel E. Ntiri, Melissa F. Holmes, Parisa M. Forooshani, Joel Ramirez, Fuqiang Gao, Miracle Ozzoude, Sabrina Adamo, Christopher J.M. Scott, Dar Dowlatshahi, Jane M. Lawrence-Dewar, Donna Kwan, Anthony E. Lang, Sean Symons, Robert Bartha, Stephen Strother, Jean Claude Tardif, Mario Masellis, Richard H. Swartz, Alan Moody, Sandra E. Black, Maged Goubran

Medical Biophysics Publications

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with …

Nnresting State Fmri Scanner Instabilities Revealed By Longitud Inal Phantom Scans In A Multi-Center Study, Aras Kayvanrad, Stephen R. Arnott, Nathan Churchill, Stefanie Hassel, Aditi Chemparathy, Fan Dong, Mojdeh Zamyadi, Tom Gee, Robert Bartha, Sandra E. Black, Jane M. Lawrence-Dewar, Christopher J.M. Scott, Sean Symons, Andrew D. Davis, Geoffrey B. Hall, Jacqueline Harris, Nancy J. Lobaugh, Glenda Macqueen, Cindy Woo, Stephen Strother

Medical Biophysics Publications

Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to …

Thermal Properties Of 18f-Fdg Uptake And Imaging In Positron Emission Tomography Scans Of Cancerous Cells, Carleigh R. Eagle

PANDION: The Osprey Journal of Research and Ideas

Positron Emission Tomography (PET) scans can utilize a radioactive tracer, in this case 2-deoxy2-[fluorine-18] fluoro-D-glucose (¹⁸F-FDG), to visualize malignant tumors in cancer patients. The uptake was compared to glucose to understand the difference in thermal properties, which contribute to the ability to image the cancerous cells. The uptake of ¹⁸F-FDG by cancer cells and the imaging process of positron emission tomography were reviewed from a thermodynamic perspective. Gastrointestinal and neurological imaging techniques were reviewed to understand the role of PET imaging in different areas of the human body.